Significance Disorders of normal kidney development represent a major cause of renal failure and end stage renal disease (ESRD) in the pediatric population. Congenital anomalies such as prenatal urinary tract obstructions can have significant effects on renal function postnatally. Although congenital obstructive nephropathy is a major cause of chronic renal failure, little progress has been made towards understanding pathophysiologic mechanism(s) and developing methods for prevention and treatment. Objectives In order to further our understanding of the prenatal pathogenesis of renal dysplasia, develop markers to predict postnatal compromise and disease, and design interventive strategies for improving the outcome of obstructive nephropathy and renal dysplasia, a fetal monkey model that closely parallels human development and disease is being studied. Results An ultrasound-guided technique has been developed for inducing unilateral ureteral obstruction in the fetal monkey during the early second trimester, when active nephrogenesis is in progress. In utero renal anatomical and hemodynamic changes, and effects on fetal urine and amniotic fluid volume and biochemistry are monitored post-obstruction. Both non-obstructed and obstructed fetal monkey kidneys are studied to evaluate the histopathologic progression of obstructive nephropathy, and to determine the pattern of expression of insulin-like growth factor (IGF) genes and apoptotic markers. Initial studies have shown that the expression of IGF and IGF binding protein (IGFBP) mRNAs in the fetal monkey kidney are identical to that in human under normal developmental conditions. Since preliminary evidence suggests that the histopathologic progression of multicystic renal dysplasia includes an alteration in the pattern of expression of IGF-II, IGFBP-2, and IGFBP-3, this implies that IGF and IGFBP gene expression is intimately associated with the development and progression of multicystic dysplastic changes over time. Future Directions To characterize the developmental changes associated with obstruction, and investigate novel in utero approaches for reversing and/or preventing the abnormalities associated with disease. KEYWORDS fetus, kidney, IGF-II, IGFBP-3, apoptosis, obstructive uropathy